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新型及新兴的低密度脂蛋白胆固醇降低策略:血脂异常管理的新时代。

Novel and Emerging LDL-C Lowering Strategies: A New Era of Dyslipidemia Management.

作者信息

Agnello Federica, Ingala Salvatore, Laterra Giulia, Scalia Lorenzo, Barbanti Marco

机构信息

Division of Cardiology, Ospedale Umberto I, ASP 4 di Enna, 94100 Enna, Italy.

Faculty of Medicine and Surgery, Università degli Studi di Enna "Kore", 94100 Enna, Italy.

出版信息

J Clin Med. 2024 Feb 22;13(5):1251. doi: 10.3390/jcm13051251.

Abstract

Atherosclerotic cardiovascular disease (ASCVD) represents a major global health challenge, significantly contributing to mortality rates. This chronic inflammatory condition affecting blood vessels is intricately linked to hypercholesterolemia, with elevated levels of low-density lipoprotein cholesterol (LDL-C) recognized as a central and modifiable risk factor. The effectiveness of lipid-lowering therapy (LLT) in mitigating ASCVD risk is well established, with studies revealing a substantial reduction in major ischemic events correlating with LDL-C reduction. While statins, often combined with ezetimibe, remain fundamental in dyslipidemia management, a significant proportion of patients on statin therapy continue to experience cardiovascular events. Recent pharmacological advancements, driven by a deeper understanding of atherogenesis, have unveiled novel therapeutic targets and potent drugs. Notably, agents like bempedoic acid and proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors (evolocumab, alirocumab, inclisiran) have emerged as effective options to intensify LLT and achieve LDL-C goals, addressing limitations associated with statins, such as myopathy. Molecular insights into alternative pathways have spurred the investigation of emerging agents, offering promising perspectives for novel medications with efficacy comparable to established treatments, associated with advantages in cost and administration. This review provides a comprehensive overview of the evolving landscape of lipid-lowering strategies, highlighting the progress made in addressing ASCVD risk and the potential of upcoming therapies to further optimize cardiovascular prevention.

摘要

动脉粥样硬化性心血管疾病(ASCVD)是一项重大的全球健康挑战,对死亡率有重大影响。这种影响血管的慢性炎症性疾病与高胆固醇血症密切相关,低密度脂蛋白胆固醇(LDL-C)水平升高被认为是一个核心且可改变的风险因素。降低血脂治疗(LLT)在降低ASCVD风险方面的有效性已得到充分证实,研究表明主要缺血事件的大幅减少与LDL-C的降低相关。虽然他汀类药物(通常与依折麦布联合使用)在血脂异常管理中仍然是基础药物,但相当一部分接受他汀类治疗的患者仍会发生心血管事件。随着对动脉粥样硬化发生机制的深入了解,近期的药理学进展揭示了新的治疗靶点和强效药物。值得注意的是,贝派地酸和前蛋白转化酶枯草溶菌素/kexin 9型(PCSK9)抑制剂(依洛尤单抗、阿利西尤单抗、英克西兰)等药物已成为强化LLT并实现LDL-C目标的有效选择,解决了与他汀类药物相关的局限性,如肌病。对替代途径的分子洞察推动了对新兴药物的研究,为疗效与现有治疗相当、在成本和给药方面具有优势的新型药物提供了有前景的展望。本综述全面概述了降脂策略的不断演变,强调了在应对ASCVD风险方面取得的进展以及即将出现的疗法在进一步优化心血管预防方面的潜力。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/bfeb/10931739/95d7b4a9babb/jcm-13-01251-g001.jpg

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